Development of a ratiometric time-resolved luminescence sensor for pH based on lanthanide complexes

Time-resolved luminescence bioassay technique using lanthanide complexes as luminescent probes/sensors has shown great utilities in clinical diagnostics and biotechnology discoveries. In this work, a novel terpyridine polyacid derivative that can form highly stable complexes with lanthanide ions in aqueous media, (4′-hydroxy-2,2′:6′,2′′-terpyridine-6,6′′-diyl) bis(methylenenitrilo) tetrakis(acetic acid) (HTTA), was designed and synthesized for developing time-resolved luminescence pH sensors based on its Eu³⁺ and Tb³⁺ complexes. The luminescence characterization results reveal that the luminescence intensity of HTTA–Eu³⁺ is strongly dependent on the pH values in weakly acidic to neutral media (pK_a = 5.8, pH 4.8–7.5), while that of HTTA–Tb³⁺ is pH-independent. This unique luminescence response allows the mixture of HTTA–Eu³⁺ and HTTA–Tb³⁺ (the HTTA–Eu³⁺/Tb³⁺ mixture) to be used as a ratiometric luminescence sensor for the time-resolved luminescence detection of pH with the intensity ratio of its Tb³⁺ emission at 540 nm to its Eu³⁺ emission at 610 nm, I_540 nm/I_610 nm, as a signal. Moreover, the UV absorption spectrum changes of the HTTA–Eu³⁺/Tb³⁺ mixture at different pHs (pH 4.0–7.0) also display a ratiometric response to the pH changes with the ratio of absorbance at 290 nm to that at 325 nm, A_290 nm/A_325 nm, as a signal. This feature enables the HTTA–Eu³⁺/Tb³⁺ mixture to have an additional function for the pH detection with the absorption spectrometry technique. For loading the complexes into the living cells, the acetoxymethyl ester of HTTA was synthesized and used for loading HTTA–Eu³⁺ and HTTA–Tb³⁺ into the cultured HeLa cells. The luminescence imaging results demonstrated the practical utility of the new sensor for the time-resolved luminescence cell imaging application.     

Hybrid materials of MCM-41 functionalized by lanthanide (Tb, Eu) complexes of modified meta-methylbenzoic acid: Covalently bonded assembly and photoluminescence

Novel organic-inorganic mesoporous hybrid materials were synthesized by linking lanthanide (Tb³⁺, Eu³⁺) complexes to the mesoporous MCM-41 through the modified meta-methylbenzoic acid (MMBA-Si) using co-condensation method in the presence of the cetyltrimethylammonium bromide (CTAB) surfactant as template. The luminescence properties of these resulting materials (denoted as Ln-MMBA-MCM-41, Ln=Tb, Eu) were characterized in detail, and the results reveal that luminescent mesoporous materials have high surface area, uniformity in the ordered mesoporous structure. Moreover, the mesoporous material covalently bonded Tb³⁺ complex (Tb-MMBA-MCM-41) exhibits the stronger characteristic emission of Tb³⁺ and longer lifetime than Eu-MMBA-MCM-41 due to the triplet state energy of organic legend MMBA-Si matches with the emissive energy level of Tb³⁺ very well.     

Spectroscopic studies on the interaction of cilostazole with iodine and 2,3-dichloro-5,6-dicyanobenzoquinone

Lanthanide sensitized luminescence and chemiluminescence (CL) are of great importance because of the unique spectral properties, such as long lifetime, large Stokes shifts, and narrow emission bands characteristic to lanthanide ions (Ln³⁺). With the fluoroquinolone (FQ) compounds including enoxacin (ENX), norfloxacin (NFLX), lomefloxacin (LMFX), fleroxacin (FLRX), ofloxacin (OFLX), rufloxacin (RFX), gatifloxacin (GFLX) and sparfloxacin (SPFX), the luminescence and CL properties of Tb³⁺–FQ and Eu³⁺–FQ complexes have been investigated in this contribution. Ce⁴⁺–SO₃²⁻ in acidic conditions was taken as the CL system and sensitized CL intensities of Tb³⁺–FQ and Eu³⁺–FQ complexes were determined by flow-injection analysis. The luminescence and CL spectra of Tb³⁺–FQ complexes show characteristic peaks of Tb³⁺ at 490 nm, 545 nm, 585 nm and 620 nm. Complexes of Tb³⁺–ENX, Tb³⁺–NFLX, Tb³⁺–LMFX and Tb³⁺–FLRX display relatively strong emission intensity compared with Tb³⁺–OFLX, Tb³⁺–RFX, Tb³⁺–GFLX and Tb³⁺–SPFX. Quite weak peaks with unique characters of Eu³⁺ at 590 nm and 617 nm appear in the luminescence and CL spectra of Eu³⁺–ENX, but no notable sensitized luminescence and CL of Eu³⁺ could be observed when Eu³⁺ is added into other FQ. The distinct differences on emission intensity of Tb³⁺–FQ and Eu³⁺–FQ might originate from the different energy gap between the triplet levels of FQ and the excited levels of the Ln³⁺. The different sensitized luminescence and CL signals among Tb³⁺–FQ complexes could be attributed to different optical properties and substituents of these FQ compounds. The detailed mechanism involved in the luminescence and CL properties of Tb³⁺–FQ and Eu³⁺–FQ complexes has been investigated by analyzing the luminescence and CL spectra, quantum yields, and theoretical calculation results.     

Study of lanthanide aromatic acid complexes in silica gels by photoacoustic spectroscopy

Lanthanide complexes Ln(p-ABA)₃·H₂O (p-ABA: p-aminobenzoic acid; Ln³⁺:La³⁺, Tb³⁺ and Er³⁺) have been incorporated into silica gels via a sol–gel method. Upon heat treatment at 120 °C, photoacoustic (PA) intensity of the ligand increases for Tb³⁺, La³⁺ and Er³⁺ complexes in silica gels, respectively, while this difference cannot be observed for the samples without heat treatment. Different PA intensities of the samples are interpreted by comparison with their luminescence spectra. The nephelauxetic parameters and PA branching vectors of Er³⁺ complex in silica gel have been calculated. Spectral results indicate that p-ABA does not coordinate with lanthanide ions in silica matrix without a suitable heat treatment. For the co-doped samples, it is shown that the emissions of Tb³⁺ are enhanced with addition of La(p-ABA)₃·H₂O and remarkably quenched with the addition of Er(p-ABA)₃·H₂O. The possible mechanisms for these phenomena are proposed.     

Effect of Condensed Media on the Luminescent Characteristics of Lanthanide Complexes

The effect condensed media based on water-soluble polymers (WSPs) have on the luminescence of Eu³⁺ and Tb³⁺ complexes with derivatives of benzoic acid and β-diketones is investigated. The effect of WSPs is found to depend on the ratio between the triplet energy levels of polymers and ligands. The most intense luminescence is observed in WSP films. The possibility of a proportional increase in the intensity of Ln³⁺ luminescence in WSP solutions over a wider range of concentrations than in an aqueous solution, and of a considerable increase in Ln³⁺ luminescence in WSP solutions and films in the presence of d- and f-element quenchers, is established.     

From chemistry to materials, design and photophysics of functional terbium molecular hybrids from assembling covalent chromophore to alkoxysilanes through hydrogen transfer addition

Two silica-based organic-inorganic hybrid materials composed of phenol (PHE) and ethyl-p-hydroxybenzoate derivatives (abbreviated as EPHBA) complexes were prepared via a sol-gel process. The active hydroxyl groups of PHE/EPHBA grafted by 3-(triethoxysilyl)-propyl isocyanate (TESPIC) through hydrogen transfer reaction were used as multi-functional bridged components, which can coordinate to Tb³⁺ with carbonyl groups, strongly absorb ultraviolet and effectively transfer energy to Tb³⁺ through their triplet excited state, as well as undergo polymerization or crosslinking reactions with tetraethoxysilane (TEOS), for anchoring terbium ions to the silica backbone. For comparison, two doped hybrid materials in which rare-earth complexes were just encapsulated in silica-based sol-gel matrices were also prepared. NMR, FT-IR, UV/vis absorption and luminescence spectroscopy were used to investigate the obtained hybrid materials. UV excitation in the organic component resulted in strong green emission from Tb³⁺ ions due to an efficient ligand-to-metal energy transfer mechanism.     

Anodic stripping voltammetric determination of arsenic(III) using a glassy carbon electrode modified with gold-palladium bimetallic nanoparticles

We have developed a method for the determination of the three catecholamines (CAs) epinephrine (EP), norepinephrine (NE), and dopamine (DA) at sub-nanomolar levels. It is found that the luminescence of the complexes formed between the CAs and Tb³⁺ ion is strongly enhanced in the presence of colloidal silver nanoparticles (Ag-NPs). The Ag-NPs cause a transfer of the resonance energy to the fluorophores through the interaction of the excited-state fluorophores and surface plasmon electrons in the Ag-NPs. Under the optimized condition, the luminescence intensity of the system is linearly related to the concentration of the CAs. Linearity is observed in the concentration ranges of 2.5–110?nM for EP, 2.8–240?nM for NE, and 2.4–140?nM for DA, with limits of detection as low as 0.25?nM, 0.64?nM and 0.42?nM, respectively. Relative standard deviations were determined at 10?nM concentrations (for n?=?10) and gave values of 0.98%, 1.05% and 0.96% for EP, NE and DA, respectively. Catecholamines were successfully determined in pharmaceutical preparations, and successful recovery experiments are demonstrated for urine and serum samples.

A Lanthanide‐Complex‐Based Ratiometric Luminescent Probe Specific for Peroxynitrite

A lanthanide‐complex‐based ratiometric luminescence probe specific for peroxynitrite (ONOO^?), 4′‐(2,4‐dimethoxyphenyl)‐2,2′:6′,2′′‐terpyridine‐6,6′′‐diyl]bis(methylenenitrilo)tetrakis(acetate)‐Eu³⁺/Tb³⁺ ([Eu³⁺/Tb³⁺(DTTA)]), has been designed and synthesized. Both [Eu³⁺(DTTA)] and [Tb³⁺(DTTA)] are highly water soluble with large stability constants at ≈10²⁰, and strongly luminescent with luminescence quantum yields of 10.0 and 9.9 %, respectively, and long luminescence lifetimes of 1.38 and 0.26 ms, respectively. It was found that the luminescence of [Tb³⁺(DTTA)] could be quenched by ONOO^? rapidly and specifically in aqueous buffers, while that of [Eu³⁺(DTTA)] did not respond to the addition of ONOO^?. Thus, by simply mixing [Eu³⁺(DTTA)] and [Tb³⁺(DTTA)] in an aqueous buffer, a ratiometric luminescence probe specific for time‐gated luminescence detection of ONOO^? was obtained. The performance of [Tb³⁺(DTTA)] and [Eu³⁺/Tb³⁺(DTTA)] as the probes for luminescence imaging detection of ONOO^? in living cells was investigated. The results demonstrated the efficacy and advantages of the new ratiometric luminescence probe for highly sensitive luminescence bioimaging application.     

Development of a novel terbium(III) chelate-based luminescent probe for highly sensitive time-resolved luminescence detection of hydroxyl radical

Time-resolved (or time-gated) luminescence detection technique using lanthanide chelates as luminescent probes is a widely used and highly sensitive method for the biological applications. The developments of various functional lanthanide probes that can selectively recognize the biological targets are the essential objective of the technique. In this work, a unique Tb³⁺ chelate-based luminescent probe, N,N,N¹,N¹-[2,6-bis(3′-aminomethyl-1′-pyrazolyl)-4-(p-aminophenoxy)methylene-pyridine] tetrakis(acetate)-Tb³⁺(BMPTA-Tb³⁺), has been designed and synthesized for highly selective and sensitive time-resolved luminescence detection of one highly reactive oxygen species (ROS), hydroxyl radical (OH). The probe is almost non-luminescent, and can selectively react with hydroxyl radical to afford a highly luminescent Tb³⁺ chelate, N,N,N¹,N¹-[2,6-bis(3′-aminomethyl-1′-pyrazolyl)-4-hydroxymethyl-pyridine] tetrakis(acetate)-Tb³⁺ (BHTA-Tb³⁺), accompanied by a 49-fold increase in luminescence quantum yield with a long luminescence lifetime (2.76 ms). The luminescence response of the probe to hydroxyl radical is highly selective and insensitive to pH in the physiological pH range. For loading the probe into the living cells, the acetoxymethyl ester of BMPTA-Tb³⁺ was synthesized and used for the HeLa cell loading. Based on this probe, a background-free time-resolved luminescence imaging method for detecting hydroxyl radical in living cells was successfully established.     

Terbium sensitized luminescence for the determination of fexofenadine in pharmaceutical formulations

A sensitive and specific luminescence method for the determination of Fexofenadine (FEX), in pharmaceutical formulations is reported. The method is based on the sensitization of terbium (Tb³⁺) by complex formation with FEX. The luminescence signal for Tb–FEX complex is greatly enhanced by the addition of triethylamine (ET₃N) and zinc nitrate in methanol solution. Monitoring of the signal is accomplished when the instrument is in the phosphorescence mode with the excitation and emission wavelengths set at λ_ex = 220 nm and λ_em = 550 nm respectively. Optimum conditions for the formation of the complex in methanol were 2.25 × 10^?6 M of Tb³⁺, 5.00 × 10^?6 M of Et₃N and Zn²⁺ which allows for the determination of 10–800 ppb of FEX in the batch mode with a detection limit of 0.3 ppb. The proposed method was successfully applied for the determination of FEX in pharmaceutical formulations.     

Study on the Fluorescence System of Oxolinic Acid‐Tb(III) and the Determination of Oxolinic Acid

Abstract

In Tris‐HCl buffer (pH=7.43), Tb³⁺ can react with oxolinic acid (OA) and form a 1:2 complex, which emits the intrinsic fluorescence of Tb³⁺. Based on this, a new fluorimetric method of determination of OA is developed. Under the optimum conditions, the enhanced fluorescence intensity of the system is proportional to the concentration of OA in the range of 1.5×10^?7～2.5×10^?5mol/L, and the detection limit is 5.5×10^?9 mol/L. Recovery test was also satisfactory. The experiments indicated that the luminescence mechanism was attributed to the M*–M luminescence.     

High-performance,synergistically catalytic luminescent nanozyme for the degradation and detection of endocrine-disrupting chemical diethylstilbestrol

A synergistically catalytic luminescent nanozyme was designed and synthesized for the degradation and enzymatic fluorescence detection of diethylstilbestrol, an endocrine-disrupting environmental pollutant. Because of the integration of cocatalytic Cu²⁺ ion and CeO₂ particle, luminescent Tb³⁺ ion, and functional ligand dipicolinic acid through flexible metal-organic framework structure, this nanozyme has not only the dual functions of luminescence and multienzyme such as laccase and horseradish peroxidase but also synergistically catalytic effect via a regeneration of Cu²⁺ oxidized by CeO₂. The synergistically catalytic effect of nanozyme greatly enhances the degradation of diethylstilbestrol. The resultants sensitized the luminescence of Tb³⁺ ions, which was used to sense the pM level of diethylstilbestrol in environmental samples. Such a high-performance catalytic luminescent nanozyme can be used to replace natural enzymes for the enzyme-based degradations and ultrasensitive assays. The strategy of constructing artificial enzymes directly from functional units provides a new way for developing fit-for-purpose multifunctional artificial enzymes.     

Terpyridine-Functionalized Calixarenes: Synthesis,Characterization and Anion Sensing Applications

Lanthanide complexes have been developed and are reported herein. These complexes were derived from a terpyridine-functionalized calix[4]arene ligand, chelated with Tb³⁺ and Eu³⁺. Synthesis of these complexes was achieved in two steps from a calix[4]arene derivative: (1) amide coupling of a calix[4]arene bearing carboxylic acid functionalities and (2) metallation with a lanthanide triflate salt. The ligand and its complexes were characterized by NMR (¹H and ¹³C), fluorescence and UV-vis spectroscopy as well as MS. The photophysical properties of these complexes were studied; high molar absorptivity values, modest quantum yields and luminescence lifetimes on the ms timescale were obtained. Anion binding results in a change in the photophysical properties of the complexes. The anion sensing ability of the Tb(III) complex was evaluated via visual detection, UV-vis and fluorescence studies. The sensor was found to be responsive towards a variety of anions, and large binding constants were obtained for the coordination of anions to the sensor.     

Fluorescent and photochemical properties of TbIII complexes with acrylic acid-based macromolecular ligands

The fluorescent and photochemical properties of Tb^III complexes with macromolecular ligands based on acrylic acid were studied. The photochemical behavior of the macromolecular Th^II complexes with acrylic acid-alkyl methacrylate copolymers differs considerably from those of Tb^III complexes with polyacrylic acid and of low-molecular-weight analogs; in the former case, the intensity of Tb³⁺ photoluminescence noticeably increases during photolysis rather than decreases. It was found that the increase in the length of the alkyl group in the alkyl methacrylate favors the enhancement of the luminescence during the photolysis. The higher efficiency of the enhancement of the Eu³⁺ fluorescence during the photolysis of similar complexes of Eu³⁺ compared to the complexers of Tb³⁺ is due to the nature of the electrodipole hypersensitive⁵D₀–⁷F₂ transition in Eu³⁺.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 2007–2010, August, 1996.     

增强掺Tb凝胶玻璃荧光性能的有机螯合体的选择

采用原位合成技术, 用溶胶凝胶法制备了稀土离子(Tb^3＋), β-二酮及协同体共掺的二氧化硅玻璃, 测量了它们发射光谱和红外光谱, 并进行了XRD, SEM和TG-DSC测试. 探讨各不同成分原位合成稀土有机配合物在二氧化硅玻璃中的发光性能及热处理温度对发光性能的影响. 结果表明, 在凝胶玻璃中掺入能级较匹配的β-二酮, 可以使稀土离子的荧光增强; 合适的协同体的引用也能使稀土离子的荧光增强. 这些结果为今后制备荧光较强的含Tb离子的SiO₂凝胶玻璃提供了一定的依据.     

A Golgi Apparatus-Targetable Probe Based on Lanthanide Complexes for Ratiometric Time-Gated Luminescence Detection of Hydrogen Sulfide

Development of bioanalytical methods for selective and accurate detection of H₂S in living samples is essential for understanding the pathological and physiological functions of this gasotransmitter in biological systems. Here we report a Golgi apparatus-targetable lanthanide complex-based luminescent probe, Golgi-ABTTA-Eu³⁺/Tb³⁺, that can be used for accurately determining H₂S in aqueous solution and living cells via the ratiometric time-gated luminescence (RM-TGL) technique. This probe is composed of 2,2′:6′,2′′-terpyridine-Eu³⁺/Tb³⁺ mixed complexes as the luminophore, 4-azidobenzyl-ether as the responsive moiety, and sulfanilamide as the Golgi apparatus-targeting moiety. Upon reaction with H₂S, accompanied by the cleavage of 4-azidobenzyl group from the probe molecule, the long-lived emission of Tb³⁺ complex at 540 nm is significantly enhanced, while that of Eu³⁺ complex at 610 nm is obviously reduced. It was noted that the I₅₄₀/I₆₁₀ ratio increased by 8.8 times after the probe was exposed to H₂S, which enabled H₂S to be detected with RM-TGL method. After being incubated with living cells, the probe molecules were selectively accumulated in the Golgi apparatus, which allowed H₂S in the Golgi apparatus to be successfully imaged in RM-TGL mode.     

Photophysical Properties of Lanthanide (Eu3+, Tb3+) Hybrid Soft Gels of Double Functional Linker of Ionic Liquid–Modified Silane

Four kinds of luminescent hybrid soft gels have been assembled by introducing the lanthanide (Eu³⁺, Tb³⁺) tetrakis β‐diketonate into the covalently bonded imidazolium‐based silica through electrostatic interactions. Here, the imidazolium‐based silica matrices are prepared from imidazolium‐derived organotriethoxysilanes by the sol–gel process, in which the imidazolium cations are strongly anchored within the silica matrices while anions can still be exchanged following application for functionalization of lanthanide complexes. The photoluminescence measurements indicated that these hybrid soft gels exhibit characteristic red and green luminescence originating from the corresponding ternary lanthanide ions (Eu³⁺, Tb³⁺). Further investigation of photophysical properties reveals that these soft gels have inherited the outstanding luminescent properties from the lanthanide tetrakis β‐diketonate complexes such as strong luminescence intensities, long lifetimes and high luminescence quantum efficiencies.     

Photophysical properties of lanthanide complexes with 5-nitro-1,10-phenanthroline

Abstract  

Five novel lanthanide (Eu³⁺, Tb³⁺, Sm³⁺, Dy³⁺, and Gd³⁺) complexes with 5-nitro-1,10-phenanthroline (phenNO₂) have been synthesized and characterized by elemental analysis, IR, UV, and luminescence spectra. The triplet state energy of phenNO₂ was determined to be 20,048 cm⁻¹ via the phosphorescence spectra of phenNO₂ and its gadolinium complex. The photophysical properties of these complexes indicated that the triplet state energy of the ligand is suitable for the sensitization of the luminescence of Eu³⁺ and Sm³⁺, especially the former.     

Terbium luminescence studies of binding of adriamycin and cisplatin to tumorigenic cells

The luminescent properties of terbium ions are used to investigate the interaction of adriamycin and cisplatin with GH3/B6 pituitary tumor cells. Clinically relevant concentrations of adriamycin were found to quench the intensity (IC₅₀ = 0.6 μM) and excited-state lifetime (τ/τ₀ = 0.73) of the Tb³⁺—GH3/B6 complex. Inspection of the Tb³⁺—GH3/B6 emission spectrum and the visible absorption spectrum of adriamycin strongly strongly suggests that the quenching of Tb³⁺ luminescence by adriamycin is due to dipole-dipole resonant energy transfer; and, according to Forster's theory (R₀ = 33.6 Å), the adriamycin receptor site is located ca. 40 Å away from the bound probe, at the lipid/protein interface. The quenching of Tb³⁺ luminescence by cisplatin is best explained by a static energy-exchange mechanism; in that the cisplatin receptor site is contiguous with the Tb³⁺ binding site at the outer surface of the membrane. The data suggest that, in the plasma membrane of tumorigenic cells, the adriamycin and ciplatin receptor sites are intimately associated with the same calcium-binding protein.